The present invention relates to a process for synthesizing carbapenem intermediates and compounds.
The carbapenems are among the most broadly effective antibiotics making them useful in the treatment of a wide range of bacterial infections. The continuing emergence of bacteria exhibiting resistance to existing therapeutic agents has made development of new carbapenems an important part of our strategy in addressing this problem.
The process developed for the manufacture of the carbapenem antibiotics disclosed herein is known to make use of a palladium-catalyzed hydrogenolysis of a p-nitrobenzyl ester. The reaction is conducted at pH 6.5 to 8.5 to minimize degradation of the product. Filtration in this pH range to remove the solid catalyst following the reaction results in a solution containing unacceptably high levels of palladium. This problem has been solved in the past by adjusting the pH to below 6 prior to filtration. This pH adjustment, however, results in degradation of the product and introduces salts, which must be removed prior to isolation of the product.
This invention relates to a process that utilizes prereduced catalysts to achieve a significantly lower level of solubilized metal derived from the catalyst following the reaction.